Abstract：Objective：To observe the effect of hot compress with Huoluo Quhan Decoction combined with western medicine on pain，motor function，and the level of serum chondroitin sulfate-846 (CS-846) in patients with knee osteoarthritis. Methods：A total of 138 cases of patients with knee osteoarthritis were divided into the observation group and the control group according to the random number table method， with 69 cases in each group. The control group was treated with conventional western medicine，and the observation group was additionally treated with hot compress with Huoluo Quhan Decoction based on the treatment of the control group. The scores of Visual Analogue Scale (VAS) for pain evaluation，the Western Ontario and McMaster Universities Arthritis Index (WOMAC)，and Lequesne indexes，and serum CS-846 levels were compared between the two groups before and after treatment. Clinical effects and adverse reactions were compared between the two groups. Results： After treatment， VAS scores in the two groups were declined (P＜0.05)，and the score in the observation group was lower than that in the control group (P＜0.05). After treatment，WOMAC scores and Lequesne scores in the two groups were decreased (P＜0.05)， and the scores in the observation group were lower than those in the control group (P＜0.05). After treatment，levels of CS-846 in serum in the two groups were descended (P＜0.05)，and the level in the observation group was lower than that in the control group (P＜0.05). The total effective rate was 95.65% in the observation group，higher than that of 84.06% in the control group (P＜0.05). There was no significant difference being found in the incidence of adverse reactions between the two groups (P＞0.05). Conclusion：Hot compress with Huoluo Quhan Decoction combined with western medicine can effectively relieve pain and improve motor function of patients with knee osteoarthritis， and reduce serum CS-846 levels，with good curative effects and high safety.